Different kinetics of blimp-1 induction in B cell subsets revealed by reporter gene.

K Fairfax, LM Corcoran, Clare Pridans, ND Huntington, A Kallies, SL Nutt, DM Tarlinton

Research output: Contribution to journalArticlepeer-review

Abstract

The transcriptional repressor Blimp-1 (B lymphocyte-induced maturation protein 1) has been described as a "master regulator" of B cell differentiation into Ab-secreting cells (ASCs). Although there is mounting evidence for the importance and necessity of Blimp-1 in plasma cell development, there is uncertainty as to the role it plays in B cell differentiation of B cell subsets and the way in which it may interact with other transcription factors such as Pax5 and Bcl6 during ASC differentiation. Using a mouse expressing GFP under the control of the Blimp-1 regulatory elements (Blimp-1(GFP/+)), we examined the kinetics of Blimp-1 up-regulation in purified B cell subsets following activation. B1 cells showed the most rapid and pronounced up-regulation of Blimp-1 in response to the mitogens tested, followed by marginal zone B cells and then conventional B2 cells. Interestingly, only B1 cells substantially up-regulated Blimp-1 expression in response to CpG. B1 cells secreted negligible Ig upon isolation but were able to up-regulate Blimp-1 and initiate Ig secretion within 28 h of stimulation. Also of interest, B1 cells have a transcriptional factor profile that is intermediate between a naive B cell and an ASC, indicative of the semiactivated state of B1 cells. Transferred naive Blimp-1(GFP/+) B1 and B2 cells both gave rise to ASCs in the bone marrow, suggesting no intrinsic barriers to B1 cell entry into the long-lived ASC compartment.
Original languageEnglish
Pages (from-to)4104-4111
JournalJournal of Immunology
Volume178
Issue number7
Publication statusPublished - 2007

Keywords

  • Animals
  • B-Cell-Specific Activator Protein/genetics
  • B-Cell-Specific Activator Protein/metabolism
  • B-Lymphocyte Subsets/drug effects
  • B-Lymphocyte Subsets/immunology
  • Bone Marrow/immunology
  • Cell Differentiation/genetics
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism
  • Genes, Reporter/genetics
  • Green Fluorescent Proteins/analysis
  • Green Fluorescent Proteins/genetics
  • Immunoglobulins/immunology
  • Kinetics
  • Lymphocyte Activation/genetics
  • Mice
  • Mice, Mutant Strains
  • Regulatory Elements, Transcriptional
  • Repressor Proteins/genetics
  • Repressor Proteins/metabolism
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Up-Regulation

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